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Serum IFN (serum + ifn)

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Medical Sciences	100%

Selected Abstracts

Suppression of hepatocellular carcinoma by transplantation of ex-vivo immune-modulated NKT lymphocytes

INTERNATIONAL JOURNAL OF CANCER, Issue 3 2005
Maya Margalit
Abstract NKT cells are a regulatory subset of T lymphocytes with immune modulatory effects and an important role in anti-tumor immunity. The feasibility of "ex-vivo education" of NKT cells has recently been demonstrated. To evaluate the anti-tumor effect of ex-vivo immune-modulated NKT lymphocytes in a murine model of hepatocellular carcinoma. Athymic Balb/C mice were sublethally irradiated and transplanted with human Hep3B HCC. NKT cells prepared from immunocompetent Balb/C mice were pulsed ex vivo with HCC-derived antigens (Group A), Hep3B cells (group B) or BSA (group C), and adoptively transferred into HCC harboring mice (1 × 06 NKT cells per mouse). Group D mice did not undergo NKT cell transplantation. Group E mice were transplanted with 1 × 106 NKT cells from HBV-immunized donors. Mice were followed for tumor size and weight. To determine the mechanism of the anti-tumor effect, intrasplenic lymphocyte populations were analyzed by FACS for NKT, CD4+ and CD8+ lymphocyte subpopulations; STAT 1, 4 and 6 expression in splenocytes was assessed by Western blot, and serum cytokine levels were measured by ELISA. Adoptive transfer of NKT cells pulsed with HCC-derived antigens (group A) and NKT cells from immunized donors (group E) resulted in complete disappearance of tumors within 4 weeks and attenuated weight loss (6.5% and 7% in groups A and E, respectively). In contrast, mice in groups B, C, and D developed large, necrotic tumors and severe weight loss (21%, 17% and 23% weight loss in groups B, C, and D, respectively). NKT/CD4 and CD8/CD4 ratios were significantly increased in groups A and E (12.3 and 17.6 in groups A and D, respectively, compared to 6.4, 4.8 and 5.6 in groups B, C and D, respectively, for the NKT/CD4 ratio; 41 and 19.8 in groups A and E, respectively, compared to 6.5, 11.8 and 3.2 in groups B, C, and D, respectively, for the CD8/CD4 ratio). Expression of the transcription factor STAT4 was evident in group A, but not in groups B-D. Serum IFN,, IL12 and IL4 levels were increased in groups A and E. Adoptive transfer of NKT lymphocytes exposed ex vivo by HCC-derived antigens loaded on dendritic cells and NKT cells from immunized donors led to suppression of HCC in mice. NKT-mediated anti-tumor activity was associated increased NKT and CD8+ T lymphocyte numbers, increased expression of STAT4, a marker for IL-12 activity and elevated serum levels of the proinflammatory cytokines IFN, and IL12, and of IL4. Ex-vivo modulation of NKT lymphocytes holds promise as a novel mode of immune therapy for HCC. © 2005 Wiley-Liss, Inc. [source]

Elevated serum interferon-, activity in juvenile dermatomyositis: Associations with disease activity at diagnosis and after thirty-six months of therapy

ARTHRITIS & RHEUMATISM, Issue 6 2009
Timothy B. Niewold
Objective Interferon-, (IFN,) has been implicated in the pathogenesis of juvenile dermatomyositis (DM). The aim of this study was to examine serum IFN, activity in a cohort of children with juvenile DM to determine relationships between IFN, and indicators of disease activity and severity. Methods Thirty-nine children with definite/probable juvenile DM were included in the study. Serum samples were obtained at the time of diagnosis from 18 untreated patients with juvenile DM. Second samples from 11 of these patients were obtained at 24 months, while they were receiving treatment, and third samples were obtained from 7 of these patients at 36 months. The remaining 21 children were studied 36 months after their initial diagnosis. Serum IFN, activity was measured using a functional reporter cell assay. Results Patients with juvenile DM had higher serum IFN, activity than both pediatric and adult healthy control subjects. In untreated patients, serum IFN, activity was positively correlated with serum muscle enzyme levels (P < 0.05 for creatine kinase, aspartate aminotransferase, and aldolase) and inversely correlated with the duration of untreated disease (P = 0.017). The tumor necrosis factor , ,308A allele was associated with higher serum IFN, levels only in untreated patients (P = 0.030). At 36 months, serum IFN, levels were inversely correlated with muscle enzyme levels in those patients still requiring therapy and with the skin Disease Activity Score in those patients who had completed therapy (P = 0.002). Conclusion Serum IFN, activity was associated with higher serum levels of muscle-derived enzymes and a shorter duration of untreated disease in patients with newly diagnosed juvenile DM and was inversely correlated with measures of chronic disease activity at 36 months postdiagnosis. These data suggest that IFN, could play a role in disease initiation in juvenile DM. [source]

Age- and sex-related patterns of serum interferon-, activity in lupus families

ARTHRITIS & RHEUMATISM, Issue 7 2008
Timothy B. Niewold
Objective Interferon-, (IFN,) levels are elevated in many patients with systemic lupus erythematosus (SLE) and may play a primary role in its pathogenesis. The purpose of this study was to determine whether serum IFN, activity in SLE patients and their healthy first-degree relatives is highest in early adulthood, when the incidence of SLE is greatest. Methods Serum samples from 315 SLE patients, 359 healthy first-degree relatives, and 141 healthy unrelated donors were measured for IFN, activity using a functional reporter cell assay. IFN, activity was analyzed in relation to age, and subgroups with high levels of IFN, activity were identified within the large data sets using a Mann-Whitney sliding window segmentation algorithm. The significance of each subgrouping was ranked by Kruskal-Wallis testing. Results Age was inversely correlated with IFN, activity in female SLE patients (r = ,0.20, P = 0.001) as well as their healthy female first-degree relatives (r = ,0.16, P = 0.02). In male patients and their healthy male first-degree relatives, there was no significant overall correlation between age and serum IFN, activity. The segmentation algorithm revealed significantly increased IFN, activity between the ages of 12 and 22 years in female SLE patients and between the ages of 16 and 29 years in male SLE patients. Both male and female healthy first-degree relatives had significantly decreased IFN, activity after the age of 50 years. Conclusion Serum IFN, activity is higher in younger individuals in the SLE family cohorts, and this tendency is accentuated in affected individuals. This age-related pattern of IFN, activity may contribute to the increased incidence of SLE in early adulthood, and interestingly, males and females had similar age-related patterns of IFN, activity. [source]

Elevated serum interferon-, activity in juvenile dermatomyositis: Associations with disease activity at diagnosis and after thirty-six months of therapy

The PTPN22 C1858T polymorphism is associated with skewing of cytokine profiles toward high interferon-, activity and low tumor necrosis factor , levels in patients with lupus

ARTHRITIS & RHEUMATISM, Issue 9 2008
Silvia N. Kariuki
Objective The C1858T polymorphism in PTPN22 has been associated with the risk of systemic lupus erythematosus (SLE) as well as multiple other autoimmune diseases. We have previously shown that high serum interferon-, (IFN,) activity is a heritable risk factor for SLE. The aim of this study was to determine whether the PTPN22 risk variant may shift serum cytokine profiles to higher IFN, activity, resulting in risk of disease. Methods IFN, was measured in 143 patients with SLE, using a functional reporter cell assay, and tumor necrosis factor , (TNF,) was measured by enzyme-linked immunosorbent assay. The rs2476601 single-nucleotide polymorphism in PTPN22 (C1858T) was genotyped in the same patients. Patients were grouped, using a clustering algorithm, into 4 cytokine groups (IFN, predominant, IFN, and TNF, correlated, TNF, predominant, and both IFN, and TNF, low). Results SLE patients carrying the risk allele of PTPN22 had higher serum IFN, activity than patients lacking the risk allele (P = 0.027). TNF, levels were lower in carriers of the risk allele (P = 0.030), and the risk allele was more common in patients in the IFN,-predominant and IFN, and TNF,-correlated groups as compared with patients in the TNF,-predominant and both IFN, and TNF,-low groups (P = 0.001). Twenty-five percent of male patients carried the risk allele, compared with 10% of female patients (P = 0.024); however, cytokine skewing was similar in both sexes. Conclusion The autoimmune disease risk allele of PTPN22 is associated with skewing of serum cytokine profiles toward higher IFN, activity and lower TNF, levels in vivo in patients with SLE. This serum cytokine pattern may be relevant in other autoimmune diseases associated with the PTPN22 risk allele. [source]